Medical Center, Department of Hematology & Oncology, University of Tuebingen, Tuebingen, Germany.
Haematologica. 2012 Oct;97(10):1523-31. doi: 10.3324/haematol.2011.059378. Epub 2012 Apr 4.
We report a prospective multicenter phase II study of haploidentical hematopoietic stem cell transplantation using CD3/CD19-depleted grafts after reduced intensity conditioning with fludarabine, thiotepa, melphalan and OKT-3.
Sixty-one adults with a median age of 46 years (range 19-65 years) have been enrolled. Diagnoses were acute myeloid leukemia (n=38), acute lymphoblastic leukemia (n=8), non-Hodgkin's lymphoma (n=6), myeloma (n=4), chronic myeloid leukemia (n=3), chronic lymphatic leukemia (n=1) and myelodysplastic syndrome (n=1). Patients were considered high risk because of refractory disease (n=18), cytogenetics (n=6), complete remission (≥ 2) (n=9), chemosensitive relapse in partial remission (n=4) or relapse after prior hematopoietic stem cell transplantation (n=15 allogeneic, n=8 autologous, n=1 both). At haploidentical hematopoietic stem cell transplantation, 30 patients were in complete remission and 31 in partial remission. Grafts contained a median of 7.0 × 10(6) (range 3.2-22) CD34(+) cells/kg, 4.2 × 10(4) (range 0.6-44) CD3(+) T cells/kg and 2.7 × 10(7) (range 0.00-37.3) CD56(+) cells/kg.
Engraftment was rapid with a median of 12 days to granulocytes more than 0.5 × 10(9)/L (range 9-50 days) and 11 days to platelets more than 20 × 10(9) (range 7-38 days). Incidence of grade IIIV acute graft-versus-host-disease and chronic graft-versus-host-disease was 46% and 18%, respectively. Non-relapse mortality on Day 100 was 23% and 42% at two years. Cumulative incidence of relapse/progression at two years was 31%. Kaplan-Meier estimated 1-year and 2-year overall survival with median follow up of 869 days (range 181-1932) is 41% and 28%, respectively.
This regimen allows successful haploidentical hematopoietic stem cell transplantation with reduced intensity conditioning in high-risk patients lacking a suitable donor. (clinicaltrials.gov identifier:NCT00202917).
我们报告了一项前瞻性、多中心 II 期研究，在接受氟达拉滨、噻替哌、马法兰和 OKT-3 预处理的情况下，使用 CD3/CD19 耗尽的移植物进行单倍体相合造血干细胞移植。
61 名中位年龄为 46 岁（19-65 岁）的成年人入组。诊断为急性髓细胞白血病（n=38）、急性淋巴细胞白血病（n=8）、非霍奇金淋巴瘤（n=6）、骨髓瘤（n=4）、慢性髓细胞白血病（n=3）、慢性淋巴细胞白血病（n=1）和骨髓增生异常综合征（n=1）。由于难治性疾病（n=18）、细胞遗传学（n=6）、完全缓解（≥2）（n=9）、部分缓解时化疗敏感复发（n=4）或既往造血干细胞移植后复发（均为同种异体移植 n=15、自体移植 n=8、双次移植 n=1），患者被认为是高危患者。在单倍体相合造血干细胞移植时，30 名患者处于完全缓解，31 名患者处于部分缓解。移植物中含有中位数为 7.0×10^6（范围 3.2-22）个 CD34+细胞/kg、4.2×10^4（范围 0.6-44）个 CD3+T 细胞/kg 和 2.7×10^7（范围 0.00-37.3）个 CD56+细胞/kg。
植入快速，中性粒细胞计数超过 0.5×10^9/L 的中位数时间为 12 天（范围 9-50 天），血小板计数超过 20×10^9/L 的中位数时间为 11 天（范围 7-38 天）。III/IV 级急性移植物抗宿主病和慢性移植物抗宿主病的发生率分别为 46%和 18%。第 100 天非复发死亡率为 23%，两年时为 42%。两年时累积复发/进展率为 31%。Kaplan-Meier 估计，中位随访 869 天（范围 181-1932）后，1 年和 2 年的总生存率分别为 41%和 28%。
在缺乏合适供体的高危患者中，这种方案允许使用低强度预处理的单倍体相合造血干细胞移植成功。（临床试验标识符：NCT00202917）。
